A synthetic equivalent for

Guitian et al. reported a total synthesis of ellipticine (228) using a modified Gribble methodology (722,723). This approach applied 2-chloro-3,4-pyridyne (1267) as a synthetic equivalent for 3,4-pyridyne and used the polar effect of the chlorine atom for improved yields and regiocontrol of the cycloaddition with the furoindole 544. Silylation of 2-chloro-3-hydroxypyridine (1263), followed by treatment of 1264 with LDA, afforded the 4-trimethylsilylpyridine 1265. This reaction probably involves... 

More recently, Pirrung and co-workers established the facility with which the Rh2(OAc)4 catalyzed reaction of 2-diazocyclohexane-l,3-dione (306) and its substituted derivatives (Scheme 8.76) occurs with dihydrofuran and dihydropyran (351-353), vinyl acetates (354) (306 307), terminal alkynes (355) (306 308), methoxyallene (355), trimethylsilylketene (serving as a synthetic equivalent for ketene) (355), and heteroaromatic compounds (353). This reaction is quite useful... 

An alio-threonine analogue was prepared in this way. The Nebraska group has also explored the use of diallyl phosphonates driven by the need to develop mild deprotection methods [77]. Treatment of ketophosphonates with alkoxide base led to the formation of difluoroenolates and thus difluoromethylketones [78]. The lithiophosphate then acts as a synthetic equivalent for the difluoro-methyl anion synthon (Eq. 21). 

In a straightforward refinement of their concept Rubin et al. have turned to cyclophyne 14 [32] in which the vinylic hydrogens of 13 are replaced by 1,2-dioxocyclobuteno groups. This cyclic diketone moiety has been used previously [18, 33, 34] as a synthetic equivalent for alkynyl groups which can be generated from the dione by thermally or photochemically induced CO expulsion. Successive decarbonylation of 14 should ultimately lead to cyclophyne 15 with the composition Q0H6. 

Alkynes are readily hydrocyanated in the presence of a homogeneous catalyst, especially a nickel-based catalyst system. However, zerovalent palladium compounds are reported to catalyze the reaction as well, but are less efficient [60], The reaction gives an easy access to the synthetically valuable a,P-un-saturated nitriles. The use of acetone cyanohydrin as a synthetic equivalent for the difficult-to-handle HCN provides an efficient alternative, but the substrate/ catalyst ratio has to be increased in comparison with the reaction with HCN. The regioselectivity of the reaction is controlled by steric, electronic, and chelative effects. Investigations were predominantly performed by changing the substituent pattern on the acetylenic substrate [61]. 

Diels-Alder reactions. The reagent undergoes [4-i-2]cycloadditions to give adducts bearing an alkenylstannane moiety. Accordingly, it can be considered as a synthetic equivalent for acetylene and substituted alkynes (aryl, acyl, and haloalkynes). 

In this section, the specific behavior of methylenecyclopropane as a synthetic equivalent for trimethylenemethane is discussed. The variability of reaetivity, as well as ehemo-, regio-and diastereoseleetivity patterns with respect to catalysts and substrates, is demonstrated. Some aspeets of these topics have been reviewed. " ... 

The vinyl and allyl trimethylsilanes obtained in the course of these cycloaddition reactions can be readily desilylated by protolysis, e.g. using excess trifluoroacetic acid (TFA) in di-chloromethane at 0°C. The corresponding desilylated alkenes are formed in high yield along with minor amounts of isomerization products, as exemplified for the isomeric hexahydropcn-talen-l(2//)-one derivatives 14 and 15. The silyl-substituted MCP can thus be employed as a synthetic equivalent for the parent MCP. 

The synthesis of diethyl ethynylphosphonate has recently been described using lithium few(diisopropyl unino)boracetylide as a synthetic equivalent for lithium acetylide. After reaction with diethyl chlorophosphate in THF at -TS C, the protected diethyl ethynylphosphonate is hydrolyzed with a 3 M1 ICl solution to produce diethyl ethynylphosphonate in good overall yield (72%), comparable with those previously obtained (Scheme I.IO). Synthesis of diethyl ethynylphosphonate has also been reported with an overall yield of 68% by a three-step synthesis including the reaction of lithium trimethylsilylacetylide with diethyl chlorophosphite (83%) followed by oxidation with MCPBA and deprotection with KF in EtOH (82%). ... 

Matthews, D.P, Gross, R.S., and McCarthy, J.R., A new route to 2-fluoro-l-olefins utilizing a synthetic equivalent for the 1-fluoroethene anion. Tetrahedron Lett., 35, 1027, 1994. 

The Baeyer-Villiger reaction has solved a regioselectivity problem here. L-tyrosine, a relatively cheap amino acid, can be converted to the important drug L-dopa provided it can be hydroxylated ortho to the OH group. This is where electrophilic substitutions of the phenol take place, but electrophilic substitutions with HO are not possible. However, after a Friedel-Crafts acylation, the acyl group can be converted to hydroxyl by the Baeyer-Villiger reaction and hydrolysis. The Baeyer-ViUiger reaction means that MeCO can be used as a synthetic equivalent for Note... 

Ellis and coworkers have found Ti(CO)5 (dmpe) to be much more reactive than Ti(CO)3(dmpe)2, and have found that it can serve as a synthetic equivalent for Ti(CO)7. Reaction of Ti(CO)5(dmpe) with NaCp, Naind, or K[(HB(pz)3)j leads to loss of one carbonyl and dmpe to give the corresponding anionic complexes [CpTi(CO)4 (equation 2), [IndTi(CO)4 , and [HB(pz)3Ti(CO)4 , respectively, in 70-80% yield. Treatment of Ti(CO)5(dmpe) with NaEPhs... 

In addition to recovered 456 (38%) there was obtained monoadduct 457 and, in very low yield, bis-adduct 458. Additional 458 (11%) could be obtained by resubjecting 457 to the aryne-generating conditions. Hydrogenation and thermolysis converted 458 to 459 in essentially quantitative yield. In these reactions, the 3,6-dibromoanthranilic acid functions as a synthetic equivalent for 1,3,5-benzatriyne, albeit the overall yield of 458 is very low. 

Bis-arynic reagents in which the two arynes are in separate, insulated arene rings have also been developed. For example, bis-anthranilic acid 478 is a synthetic equivalent for diaryne 479 aprotic diazotization of 478 in the presence of various dienes (i.e., tetraphenylcyclone, 2,5-dimethylfuran, anthracene) gave the expected bis-adducts in 40-... 

Finally, a double [2+2] cycloaddition with p-dibromobenzene and 1,1-dimethoxy-ethylene gave, after acid hydrolysis, a 20% yield of the novel bis-benzocyclobutenone 483. Thus p-dibromobenzene acts as a synthetic equivalent for diyne 434, and cycloaddition to the presumed intermediate aryne 484 is regioselective. 

On the face of it, the utilisation of cyclohexane-1,3-dione (121) as shown in Scheme 11 does not appear to fit the analysis presented immediately above. However, by virtue of its participation in the illustrated Michael addition reaction (120 -I- 121 —> 122) and the subsequent manipulation of adduct 122 (equivalent to a cross-coupling product) compound 121 could legitimately be viewed as a synthetic equivalent for a 2-halogeno-2-cyclohexen-l-ol. The chemical efficiency of the Michael addition reaction is notable and suggests a greater utility for this process than has been realised so far. 

Finally 4-acetoxycyclopent-2-enone (136), acting as a synthetic equivalent for non-existent cyclopenta-2,4-dienone, has been observed to undergo Michael additions, affording fran -disubstituted cyclopentanone derivatives, e.g. (137), capable of subsequent aldol cyclization to rran5-hydroazulene systems, e.g. (138). ... 

Diels-Alder reactions (with normal electron demand) rely on an electron-rich diene and an electron-deficient dienophile. As aconsequence, there exist a number of impossible dienophiles one might like to use in synthesis, which turn out to have too poor reactivity in Diels-Alder cycloadditions or which participate in alternate reaction pathways. Such impossible dienophiles are CH2=CH2, RCH=CH2, CH2=C=0, HC=CH, and RC=CH — all building blocks that one really wishes to employ in the planning of a synthesis. Fortunately, a series of synthetic equivalents for these impossible dienophiles exists. They participate readily in Diels-Alder cycloadditions, though they require subsequent refunctionalization steps. The example [28] in Scheme 6.11 demonstrates that vinylsulfone CH2=CHS02Ph may serve as a synthetic equivalent for either CH2=CH2 or RCH=CH2. 

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